P
US11027282B2ActiveUtilityPatentIndex 61

Digital to biological converter

Assignee: CODEX DNA INCPriority: Aug 16, 2012Filed: Jul 19, 2017Granted: Jun 8, 2021
Est. expiryAug 16, 2032(~6.1 yrs left)· nominal 20-yr term from priority
Inventors:VENTER J CRAIGGIBSON DANIELGILL JOHN E
C12P 19/34C12N 15/1093C12N 15/1089C12N 7/00B01L 7/52A61P 31/16A61P 31/00C07K 14/005
61
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0
Cited by
58
References
23
Claims

Abstract

The present invention provides a system for receiving biological sequence information and activating the synthesis of a biological entity. The system has a receiving unit for receiving a signal encoding biological sequence information transmitted from a transmitting unit. The transmitting unit can be present at a remote location from the receiving unit. The system also has an assembly unit connected to the receiving unit, and the assembly unit assembles the biological entity according to the biological sequence information. Thus, according to the present invention biological sequence information can be digitally transmitted to a remote location and the information converted into a biological entity, for example a protein useful as a vaccine, immediately upon being received by the receiving unit and without further human intervention after preparing the system for receipt of the information. The invention is useful, for example, for rapidly responding to viral and other biological threats that are specific to a particular locale.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. An automated system for the synthesis of a double-stranded DNA molecule according to provided biological sequence information, comprising:
 an assembly unit that assembles the double-stranded DNA molecule according to the provided biological sequence information, the assembly unit comprising or connected to vessels containing a plurality of oligonucleotide molecules and containing components that transport reagents within the system and that executes steps in an automated method for synthesizing the double-stranded DNA molecule, wherein the method comprises the assembly of one or more dsDNA molecule(s) by joining the plurality of oligonucleotides, and wherein no human intervention occurs after the method is initiated and until the double-stranded DNA molecule is synthesized; 
 and the system further comprising a non-transitory computer readable medium containing software programming instructions that direct steps in the assembly unit for the assembly of the plurality of oligonucleotide molecules into the double stranded DNA molecule in the automated method, 
 wherein the software programming instructions direct a step of PCR amplification in a first reaction zone of a reaction container, a step of error correction in a second reaction zone of a reaction container performed after the step of PCR amplification, a step of DNA assembly in a third reaction zone of a reaction container, and directs the transport of reagents from one reaction zone to the next, wherein the reaction container is a reaction plate having dimensions of about 127 mm× about 85 mm, and the reaction zones comprise one or more reaction wells on the reaction plate; and 
 wherein the system further comprises a robotic arm configured to transfer the oligonucleotide molecules from the first reaction zone to the second reaction zone, and from the second reaction zone to the third reaction zone, the sample successively accumulating in each reaction zone. 
 
     
     
       2. The automated system of  claim 1  wherein the oligonucleotides are provided to a sub-unit of the assembly unit for amplification of the oligonucleotides by the step of PCR. 
     
     
       3. The automated system of  claim 1  wherein the oligonucleotides are from 40-100 nucleotides in length. 
     
     
       4. The automated system of  claim 1  wherein the system further comprises software programming instructions and reagents directing steps for the transcription of the DNA molecule into an RNA molecule. 
     
     
       5. The automated system of  claim 4  wherein the system further comprises software programming instructions and reagents directing translation of the RNA molecule into a protein molecule. 
     
     
       6. The system of  claim 5  wherein the protein is further processed by the system to produce a virus particle or a portion of a virus particle. 
     
     
       7. The system of  claim 6  wherein the virus particle or portion of a virus particle comprises a protein antigen. 
     
     
       8. The system of  claim 1  wherein the assembly unit further comprises or is connected to a vessel comprising a host cell. 
     
     
       9. The system of  claim 1  wherein the conditions for a step are established in a reaction zone and a sample is subsequently moved into the reaction zone. 
     
     
       10. The system of  claim 1  further comprising that the software programming instructions direct an RNA transcription step performed in a reaction zone of a reaction container. 
     
     
       11. The system of  claim 1  wherein the reaction container is a 96 well plate. 
     
     
       12. The automated system of  claim 1  wherein the double stranded DNA molecule is greater than 500 bp in size. 
     
     
       13. The automated system of  claim 1  wherein the software programming instructions comprise instructions for simultaneously assembling the plurality of oligonucleotide molecules into the dsDNA molecule(s). 
     
     
       14. The automated system of  claim 2  wherein the assembly unit further comprises or is connected to vessels containing a nucleic acid molecule selected from the group consisting of: a plasmid, a vector, a regulatory sequence, a promoter sequence, a binding element for a trans-acting factor, and a signal sequence. 
     
     
       15. The automated system of  claim 1  wherein the plurality of oligonucleotide molecules are 30-110 nucleotides in length. 
     
     
       16. The automated system of  claim 1  wherein the overlapping oligonucleotides are assembled in an isothermal reaction. 
     
     
       17. The automated system of  claim 1  wherein the plurality of oligonucleotide molecules is assembled into the dsDNA molecule(s) in a simultaneous reaction. 
     
     
       18. The automated system of  claim 1  wherein the overlapping oligonucleotides are assembled in a reaction using an exonuclease and a DNA polymerase. 
     
     
       19. The automated system of  claim 1  wherein the double stranded DNA molecule is greater than 500 bp in size. 
     
     
       20. The automated system of  claim 1  wherein the error correction reaction comprises the use of a mismatch endonuclease. 
     
     
       21. The automated system of  claim 20  wherein the error correction reaction further comprises the use of exonuclease III. 
     
     
       22. The automated system of  claim 1  comprising a single reaction container. 
     
     
       23. The automated system of  claim 22  wherein the reaction container is a 96 well plate.

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